RNA-binding properties orchestrate TDP-43 homeostasis through condensate formation in vivo.

Insoluble cytoplasmic aggregate formation of the RNA-binding protein TDP-43 is a major hallmark of neurodegenerative diseases including Amyotrophic Lateral Sclerosis. TDP-43 localizes predominantly in the nucleus, arranging itself into dynamic condensates through liquid-liquid phase separation (LLPS). Mutations and post-translational modifications can alter the condensation properties of TDP-43, contributing to the transition of liquid-like biomolecular condensates into solid-like aggregates. However, to date it has been a challenge to study the dynamics of this process in vivo. We demonstrate through live imaging that human TDP-43 undergoes nuclear condensation in spinal motor neurons in a living animal. RNA-binding deficiencies as well as post-translational modifications can lead to aberrant condensation and altered TDP-43 compartmentalization. Single-molecule tracking revealed an altered mobility profile for RNA-binding deficient TDP-43. Overall, these results provide a critically needed in vivo characterization of TDP-43 condensation, demonstrate phase separation as an important regulatory mechanism of TDP-43 accessibility, and identify a molecular mechanism of how functional TDP-43 can be regulated.

ALS-linked CCNF variant disrupts motor neuron ubiquitin homeostasis.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders that share pathological features, including the aberrant accumulation of ubiquitinated protein inclusions within motor neurons. Previously, we have shown that the sequestration of ubiquitin (Ub) into inclusions disrupts Ub homeostasis in cells expressing ALS-associated variants superoxide dismutase 1 (SOD1), fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP-43). Here, we investigated whether an ALS/FTD-linked pathogenic variant in the CCNF gene, encoding the E3 Ub ligase Cyclin F (CCNF), also perturbs Ub homeostasis. The presence of a pathogenic CCNF variant was shown to cause ubiquitin-proteasome system (UPS) dysfunction in induced pluripotent stem cell-derived motor neurons harboring the CCNF  S621G mutation. The expression of the CCNFS621G variant was associated with an increased abundance of ubiquitinated proteins and significant changes in the ubiquitination of key UPS components. To further investigate the mechanisms responsible for this UPS dysfunction, we overexpressed CCNF in NSC-34 cells and found that the overexpression of both wild-type (WT) and the pathogenic variant of CCNF (CCNFS621G) altered free Ub levels. Furthermore, double mutants designed to decrease the ability of CCNF to form an active E3 Ub ligase complex significantly improved UPS function in cells expressing both CCNFWT and the CCNFS621G variant and were associated with increased levels of free monomeric Ub. Collectively, these results suggest that alterations to the ligase activity of the CCNF complex and the subsequent disruption to Ub homeostasis play an important role in the pathogenesis of CCNF-associated ALS/FTD.

Cyclin F can alter the turnover of TDP-43.

Previously, we demonstrated that the SCFcyclin F complex directly mediates the poly-ubiquitylation of TDP-43, raising the question of whether cyclin F can be used to enhance the turnover of TDP-43. A hurdle to the use of cyclin F, however, is that the overexpression of cyclin F can lead to the initiation of cell death pathways. Accordingly, the aim of this study was to identify and evaluate a less toxic variant of cyclin F. To do so, we first confirmed and validated our previous findings that cyclin F binds to TDP-43 in an atypical manner. Additionally, we demonstrated that mutating the canonical substrate region in cyclin F (to generate cyclin FMRL/AAA) led to reduced binding affinity to known canonical substrates without impacting the interaction between cyclin F and TDP-43. Notably, both wild-type and cyclin FMRL/AAA effectively reduced the abundance of TDP-43 in cultured cells whilst cyclin FMRL/AAA also demonstrated reduced cell death compared to the wild-type control. The decrease in toxicity also led to a reduction in morphological defects in zebrafish embryos. These results suggest that cyclin F can be modified to enhance its targeting of TDP-43, which in turn reduces the toxicity associated with the overexpression of cyclin F. This study provides greater insights into the interaction that occurs between cyclin F and TDP-43 in cells and in vivo.

Employment conditions and mental health of overseas female migrant domestic workers in Hong Kong: a parallel mediation analysis.

BACKGROUND: Female migrant domestic workers (MDW), approximately 8.5 million globally, often live in their employer's home under vulnerable conditions. In Hong Kong, MDWs currently comprise 5% of the population. This study was conducted to assess the association between employment conditions and mental health, and the mediating roles stress and job satisfaction have, among female MDWs in Hong Kong. METHODS: Participants completed an online cross-sectional survey. A total of 1,965 survey were collected between August 2020 and August 2021. Questions in the survey were related to MDWs background information, employment conditions, stress, job satisfaction, and two mental health outcomes: anxiety and depression. An employment conditions score was created to assess the cumulative effect poor employment conditions had on mental health. A multicategorical parallel mediation analysis was used to assess the direct effect employment conditions have on mental health and the indirect effects through stress and job satisfaction. RESULTS: Overall, 17.7% of MDWs were reported to be suffering from anxiety and 30.8% from depression. An increase in poor employment conditions was statistically associated with an increase in both outcomes, while stress levels and job satisfaction mediated this association. CONCLUSIONS: The findings call for increased scrutiny of employment conditions and mental well-being of MDWs.

Socioeconomic inequalities in psychosocial well-being among adolescents under the COVID-19 pandemic: a cross-regional comparative analysis in Hong Kong, mainland China, and the Netherlands.

BACKGROUND: Despite evidence on socioeconomic inequalities in psychosocial well-being of adolescents under the COVID-19 pandemic, the explanatory factors and their potential variations across contexts remained understudied. Hence, this cross-regional study compared the extent of inequalities and the mediating pathways across Hong Kong, Mainland China, and the Netherlands. METHODS: Between July 2021 and January 2022, 25 secondary schools from diverse socioeconomic background were purposively sampled from Hong Kong, Zhejiang (Mainland China), and Limburg (the Netherlands). 3595 junior students completed an online survey during class about their socioeconomic position, psychosocial factors, and well-being. Socioeconomic inequalities were assessed by multiple linear regressions using the Slope Index of Inequality (SII), whereas the mediating pathways through learning difficulty, overall worry about COVID-19, impact on family' financial status, resilience, trust in government regarding pandemic management, and adaptation to social distancing were examined by mediation analyses moderated by regions. RESULTS: The adverse psychosocial impact of COVID-19 was stronger in the Netherlands and Hong Kong compared with Mainland China. The greatest extent of socioeconomic inequalities in the change in psychosocial well-being was observed among students in the Netherlands (SII = 0.59 [95% CI = 0.38-0.80]), followed by Hong Kong (SII = 0.37 [0.21-0.52]) and Mainland China (SII = 0.12 [0.00-0.23]). Learning difficulty and resilience were the major mediators in Mainland China and Hong Kong, but to a lesser extent in the Netherlands. CONCLUSION: Socioeconomic inequalities in psychosocial well-being were evident among adolescents under the pandemic, with learning difficulty and resilience of students as the key mediators. Differences in the social contexts should be considered to better understand the variations in inequalities and mediating pathways across regions.

Molecular mechanisms of amyotrophic lateral sclerosis as broad therapeutic targets for gene therapy applications utilizing adeno-associated viral vectors.

Despite the devastating clinical outcome of the neurodegenerative disease, amyotrophic lateral sclerosis (ALS), its etiology remains mysterious. Approximately 90% of ALS is characterized as sporadic, signifying that the patient has no family history of the disease. The development of an impactful disease modifying therapy across the ALS spectrum has remained out of grasp, largely due to the poorly understood mechanisms of disease onset and progression. Currently, ALS is invariably fatal and rapidly progressive. It is hypothesized that multiple factors can lead to the development of ALS, however, treatments are often focused on targeting specific familial forms of the disease (10% of total cases). There is a strong need to develop disease modifying treatments for ALS that can be effective across the full ALS spectrum of familial and sporadic cases. Although the onset of disease varies significantly between patients, there are general disease mechanisms and progressions that can be seen broadly across ALS patients. Therefore, this review explores the targeting of these widespread disease mechanisms as possible areas for therapeutic intervention to treat ALS broadly. In particular, this review will focus on targeting mechanisms of defective protein homeostasis and RNA processing, which are both increasingly recognized as design principles of ALS pathogenesis. Additionally, this review will explore the benefits of gene therapy as an approach to treating ALS, specifically focusing on the use of adeno-associated virus (AAV) as a vector for gene delivery to the CNS and recent advances in the field.

Identification of phosphorylated tau protein interactors in progressive supranuclear palsy (PSP) reveals networks involved in protein degradation, stress response, cytoskeletal dynamics, metabolic processes, and neurotransmission.

Progressive supranuclear palsy (PSP) is a late-onset neurodegenerative disease defined pathologically by the presence of insoluble phosphorylated-Tau (p-Tau) in neurons and glia. Identifying co-aggregating proteins within p-Tau inclusions may reveal important insights into processes affected by the aggregation of Tau. We used a proteomic approach, which combines antibody-mediated biotinylation and mass spectrometry (MS) to identify proteins proximal to p-Tau in PSP. Using this proof-of-concept workflow for identifying interacting proteins of interest, we characterized proteins proximal to p-Tau in PSP cases, identifying >84% of previously identified interaction partners of Tau and known modifiers of Tau aggregation, while 19 novel proteins not previously found associated with Tau were identified. Furthermore, our data also identified confidently assigned phosphorylation sites that have been previously reported on p-Tau. Additionally, using ingenuity pathway analysis (IPA) and human RNA-seq datasets, we identified proteins previously associated with neurological disorders and pathways involved in protein degradation, stress responses, cytoskeletal dynamics, metabolism, and neurotransmission. Together, our study demonstrates the utility of biotinylation by antibody recognition (BAR) approach to answer a fundamental question to rapidly identify proteins in proximity to p-Tau from post-mortem tissue. The application of this workflow opens up the opportunity to identify novel protein targets to give us insight into the biological process at the onset and progression of tauopathies.

ALS/FTD-causing mutation in cyclin F causes the dysregulation of SFPQ.

Previously, we identified missense mutations in CCNF that are causative of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Hallmark features of these diseases include the build-up of insoluble protein aggregates as well as the mislocalization of proteins such as transactive response DNA binding protein 43 kDa (TDP-43). In recent years, the dysregulation of SFPQ (splicing factor proline and glutamine rich) has also emerged as a pathological hallmark of ALS/FTD. CCNF encodes for the protein cyclin F, a substrate recognition component of an E3 ubiquitin ligase. We have previously shown that ALS/FTD-linked mutations in CCNF cause disruptions to overall protein homeostasis that leads to a build-up of K48-linked ubiquitylated proteins as well as defects in autophagic machinery. To investigate further processes that may be affected by cyclin F, we used a protein-proximity ligation method, known as Biotin Identification (BioID), standard immunoprecipitations and mass spectrometry to identify novel interaction partners of cyclin F and infer further process that may be affected by the ALS/FTD-causing mutation. Results demonstrate that cyclin F closely associates with proteins involved with RNA metabolism as well as a number of RNA-binding proteins previously linked to ALS/FTD, including SFPQ. Notably, the overexpression of cyclin F(S621G) led to the aggregation and altered subcellular distribution of SFPQ in human embryonic kidney (HEK293) cells, while leading to altered degradation in primary neurons. Overall, our data links ALS/FTD-causing mutations in CCNF to converging pathological features of ALS/FTD and provides a link between defective protein degradation systems and the pathological accumulation of a protein involved in RNA processing and metabolism.

TDP-43 pathology and functional deficits in wild-type and ALS/FTD mutant cyclin F mouse models.

AIMS: Amyotrophic lateral sclerosis (ALS) is characterised by a progressive loss of upper and lower motor neurons leading to muscle weakness and eventually death. Frontotemporal dementia (FTD) presents clinically with significant behavioural decline. Approximately 10% of cases have a known family history, and disease-linked mutations in multiple genes have been identified in FTD and ALS. More recently, ALS and FTD-linked variants have been identified in the CCNF gene, which accounts for an estimated 0.6% to over 3% of familial ALS cases. METHODS: In this study, we developed the first mouse models expressing either wild-type (WT) human CCNF or its mutant pathogenic variant S621G to recapitulate key clinical and neuropathological features of ALS and FTD linked to CCNF disease variants. We expressed human CCNF WT or CCNFS621G throughout the murine brain by intracranial delivery of adeno-associated virus (AAV) to achieve widespread delivery via somatic brain transgenesis. RESULTS: These mice developed behavioural abnormalities, similar to the clinical symptoms of FTD patients, as early as 3 months of age, including hyperactivity and disinhibition, which progressively deteriorated to include memory deficits by 8 months of age. Brains of mutant CCNF_S621G mice displayed an accumulation of ubiquitinated proteins with elevated levels of phosphorylated TDP-43 present in both CCNF_WT and mutant CCNF_S621G mice. We also investigated the effects of CCNF expression on interaction targets of CCNF and found elevated levels of insoluble splicing factor proline and glutamine-rich (SFPQ). Furthermore, cytoplasmic TDP-43 inclusions were found in both CCNF_WT and mutant CCNF_S621G mice, recapitulating the key hallmark of FTD/ALS pathology. CONCLUSIONS: In summary, CCNF expression in mice reproduces clinical presentations of ALS, including functional deficits and TDP-43 neuropathology with altered CCNF-mediated pathways contributing to the pathology observed.

Sense of control as a mediator of the association between social capital and health inequality in China.

Social capital was shown to be associated with health. However, less is known about the pathways of the association and whether the mediating effect of the pathways varies across different income groups. Using adults (≥18 years) data from the 2010 Chinese General Social Survey (N = 3265), we examined the mediating effect of sense of control between social capital and health and whether income groups moderated the mediating effect in China. Health and sense of control were factor scores. Social capital measurements included frequency of socializing, civic participation, trust, and reciprocity. We categorized equivalized household income into quintiles (Q1 (lowest income) to Q5 (highest income)). Multivariable linear regression models showed that frequency of socializing (ß: 0.07; 95% CI: 0.04, 0.11), trust (ß: 0.06; 95% CI: 0.02, 0.09), and reciprocity (ß: 0.07; 95% CI: 0.03, 0.11) were positively associated with health. Moderated mediation analysis further showed that sense of control mediated the association between frequency of socializing and health in all income groups, with the mediating effect decreasing when income increased (ß (95% CI) from Q1 to Q5: 0.026 (0.015, 0.040); 0.022 (0.012, 0.036); 0.018 (0.009, 0.030); 0.013 (0.005, 0.024); 0.008 (0.000, 0.018)). Moderated mediation analysis also showed the same patterns for the mediating effect of sense of control on the association between trust and health and reciprocity and health. Our study suggested that employing social capital to promote sense of control could not only be beneficial for people's health but also be helpful to narrow the health gap on the income gradient.

Experience of South and Southeast Asian minority women in Hong Kong during COVID-19 pandemic: a qualitative study.

BACKGROUND: Hong Kong has a relatively low incidence rate of COVID-19 across the globe. Nevertheless, ethnic minorities in Hong Kong, especially South Asians (SAs) and Southeast Asians (SEAs), face numerous physical, mental, social, economic, cultural and religious challenges during the pandemic. This study explores the experiences of SA and SEA women in a predominantly Chinese metropolitan city. METHODS: Ten SA and SEA women were recruited and face-to-face interviews were conducted. Questions about participants' daily life experience, physical and mental health conditions, economic situation and social interaction amid COVID-19 pandemic were asked to assess the impact of COVID-19. RESULTS: SAs and SEAs have a distinctive family culture, and women experienced significant physical and mental impact of COVID-19 due to their unique gender role in the family. In addition to taking care of their family in Hong Kong, SA and SEA women also had to mentally and financially support family members residing in their home countries. Access to COVID-related information was restricted due to language barrier. Public health measures including social distancing imposed extra burden on ethnic minorities with limited social and religious support. CONCLUSIONS: Even when COVID-19 incidence rate is relatively low in Hong Kong, the pandemic made life even more challenging for SAs and SEAs, which is a community already struggling with language barriers, financial woes, and discrimination. This in turn could have led to greater health inequalities. Government and civil organizations should take the social determinants of health inequalities into account when implementing COVID-19-related public health policies and strategies.

Inter-Regional Proteomic Profiling of the Human Brain Using an Optimized Protein Extraction Method from Formalin-Fixed Tissue to Identify Signaling Pathways.

Proteomics offers vast potential for studying the molecular regulation of the human brain. Formalin fixation is a common method for preserving human tissue; however, it presents challenges for proteomic analysis. In this study, we compared the efficiency of two different protein-extraction buffers on three post-mortem, formalin-fixed human brains. Equal amounts of extracted proteins were subjected to in-gel tryptic digestion and LC-MS/MS. Protein, peptide sequence, and peptide group identifications; protein abundance; and gene ontology pathways were analyzed. Protein extraction was superior using lysis buffer containing tris(hydroxymethyl)aminomethane hydrochloride, sodium dodecyl sulfate, sodium deoxycholate, and Triton X-100 (TrisHCl, SDS, SDC, Triton X-100), which was then used for inter-regional analysis. Pre-frontal, motor, temporal, and occipital cortex tissues were analyzed by label free quantification (LFQ) proteomics, Ingenuity Pathway Analysis and PANTHERdb. Inter-regional analysis revealed differential enrichment of proteins. We found similarly activated cellular signaling pathways in different brain regions, suggesting commonalities in the molecular regulation of neuroanatomically-linked brain functions. Overall, we developed an optimized, robust, and efficient method for protein extraction from formalin-fixed human brain tissue for in-depth LFQ proteomics. We also demonstrate herein that this method is suitable for rapid and routine analysis to uncover molecular signaling pathways in the human brain.

The mediating role of individual-level social capital among worries, mental health and subjective well-being among adults in Hong Kong during the COVID-19 pandemic.

The COVID-19 pandemic has substantially induced worries and affected individual mental health and subjective well-being. Nonetheless, a high level of social capital could potentially protect individuals who suffer from mental health problems and thus promote their subjective well-being, especially under the social distancing policies during the pandemic. To this end, based on a random sample of 1053 Hong Kong adults, structural equation modeling was applied to study the path relationships between the worries of COVID-19, social capital, mental health problems, and subjective well-being. The study found that worries during the pandemic were associated with mental health and subjective well-being, through social capital as a mediator. Moreover, social capital exhibited a stronger influence on mental health and subjective well-being in the economically inactive group than in the economically active group. This study highlights the important role of social capital during the COVID-19 pandemic. While Hong Kong's COVID-19 response has primarily focused on disease prevention, it must be noted that social services and mutual-help activities are also crucial for people to withstand the crisis.

The converging roles of sequestosome-1/p62 in the molecular pathways of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Investigations into the pathogenetic mechanisms underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have provided significant insight into the disease. At the cellular level, ALS and FTD are classified as proteinopathies, which is motor neuron degeneration and death characterized by pathological protein aggregates or dysregulated proteostasis. At both the clinical and molecular level there are common signaling pathways dysregulated across the ALS and FTD spectrum (ALS/FTD). Sequestosome-1/p62 is a multifunctional scaffold protein with roles in several signaling pathways including proteostasis, protein degradation via the ubiquitin proteasome system and autophagy, the antioxidant response, inflammatory response, and apoptosis. Notably these pathways are dysregulated in ALS and FTD. Mutations in the functional domains of p62 provide links to the pathogenetic mechanisms of p62 and dyshomeostasis of p62 levels is noted in several types of ALS and FTD. We present here that the dysregulated ALS and FTD signaling pathways are linked, with p62 converging the molecular mechanisms. This review summarizes the current literature on the complex role of p62 in the pathogenesis across the ALS/FTD spectrum. The focus is on the underlying convergent molecular mechanisms of ALS and FTD-associated proteins and pathways that dysregulate p62 levels or are dysregulated by p62, with emphasis on how p62 is implicated across the ALS/FTD spectrum.

TDP-43 is a ubiquitylation substrate of the SCFcyclin F complex.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the loss of upper and lower motor neurons in the brain and spinal cord. ALS and frontotemporal dementia (FTD) are overlapping diseases with shared pathological features. Affected neurons of people with ALS and FTD typically contain ubiquitin-immunoreactive inclusions, of which TDP-43 (Tar DNA-binding protein of 43 kDa) is a major component. However, what triggers the formation of these abnormal TDP-43 inclusions is unclear. Previously, we identified CCNF mutations in cohorts of familial and sporadic cases of ALS and FTD. CCNF encodes cyclin F, the substrate-binding component of a multiprotein E3 ubiquitin ligase complex that ubiquitylates and subsequently directs a set of protein substrates for proteasomal degradation. Here, we explored the relationship between cyclin F and TDP-43. METHODS: We used a series of complementary biochemical approaches including immunoprecipitations, in vitro ubiquitylation assays, immunofluorescence imaging and immunocytochemistry. Unpaired student t-tests were used to determine statistical significance of the results. RESULTS: In this study, we demonstrate that that the SCFcyclin F complex directly mediates the poly-ubiquitylation of TDP-43. Importantly, we demonstrate that cyclin F bearing the pathogenic ALS/FTD mutation, S621G, leads to aberrant ubiquitylation of TDP-43 as well as the accumulation of K48-ubiquitylated TDP-43 in neuron-like cells. Furthermore, we demonstrate that a patient carrying the ALS/FTD cyclin FS195R mutation displayed skein-like cytoplasmic TDP-43 aggregates, implying abnormal TDP-43 degradation in a CCNF mutation bearing patient. CONCLUSION: In summary, this study reports a direct ubiquitylation mechanism for TDP-43, revealing important insights into the regulation of cyclin F-mediated TDP-43 turnover and clues towards understanding the molecular origins of the ubiquitylated TDP-43 inclusions that are the hallmark pathological feature in ALS and FTD.

Sociodemographic moderation of the association between depression and stroke incidence in a retrospective cohort of 0.4 million primary care recipients with hypertension.

BACKGROUND: Previous research has suggested an association between depression and subsequent acute stroke incidence, but few studies have examined any effect modification by sociodemographic factors. In addition, no studies have investigated this association among primary care recipients with hypertension. METHODS: We examined the anonymized records of all public general outpatient visits by patients aged 45+ during January 2007-December 2010 in Hong Kong to extract primary care patients with hypertension for analysis. We took the last consultation date as the baseline and followed them up for 4 years (until 2011-2014) to observe any subsequent acute hospitalization due to stroke. Mixed-effects Cox models (random intercept across 74 included clinics) were implemented to examine the association between depression (ICPC diagnosis or anti-depressant prescription) at baseline and the hazard of acute stroke (ICD-9: 430-437.9). Effect modification by age, sex, and recipient status of social security assistance was examined in extended models with respective interaction terms specified. RESULTS: In total, 396 858 eligible patients were included, with 9099 (2.3%) having depression, and 10 851 (2.7%) eventually hospitalized for stroke. From the adjusted analysis, baseline depression was associated with a 17% increased hazard of acute stroke hospitalization [95% confidence interval (CI) 1.03-1.32]. This association was suggested to be even stronger among men than among women (hazard ratio = 1.29, 95% CI 1.00-1.67). CONCLUSION: Depression is more strongly associated with acute stroke incidence among male than female primary care patients with hypertension. More integrated services are warranted to address their needs.

The role of neighborhood social capital on health and health inequality in rural and urban China.

Given the "community lost" vs. "community saved" debate on how neighborhood solidarity changes with urbanization, we compared the rural-urban difference in the association of individuals' neighborhood social capital with health and the interaction effect between neighborhood social capital and income-poverty on health in China, where huge rural-urban disparities existed. Participants were 5014 Chinese adults (≥ 18 years) (rural: 2034; urban: 2980) from the 2012 cross-sectional Chinese General Social Survey. Health outcome was a factor score constructed by three items. Neighborhood social capital was divided into structural (neighborhood network size, frequency of socializing with neighbors, voting in neighborhood committee election, and participation in neighborhood voluntary activities) and cognitive (perceived neighborhood social cohesion) dimensions. Multivariable linear regression models showed positive associations between perceived neighborhood social cohesion and health in rural (ß = 0.08, 95% CI: 0.03,0.14) and urban (ß = 0.09, 95% CI: 0.05,0.12) areas. Only in rural but not urban areas was a neighborhood network of 10 or more persons (ref.: none) associated with better health (ß = 0.25, 95% CI: 0.05,0.46). Interaction analysis showed that only in rural but not urban areas, with the increase of neighborhood network size, the health gap between the income-poor and the non-income-poor decreased generally. Our study suggested that cohesive neighborhoods benefit both rural and urban residents' health. Health interventions to improve neighborhood social cohesion should be designed to cope with the challenge of urbanization. Policymakers should avoid damaging neighborhood social capital when implementing other public policies, especially in rural areas where neighborhood network seems to matter more for health.

Explaining the Psychosocial Effects of COVID-19 Among Older Hong Kong Chinese People-A Qualitative Analysis.

BACKGROUND: Social distancing and "stay-at-home" orders are essential to contain the coronavirus outbreak; however, there are growing concerns about physical and other mental distress in older people. Apart from quantitative data, their feelings, thoughts, and experience are essential to inform the implementation of patient-centered health care policy. AIM: This study explained the psychosocial effects of COVID-19 on Hong Kong Chinese older people. DESIGN AND SETTING: This was a qualitative study. Twenty-three participants aged between 63 and 86 were recruited in primary care through purposive sampling. METHOD: Semi-structured in-depth telephone interviews were conducted to explore participants' experience during the COVID-19 pandemic. Grounded theory was used to analyze the data. RESULTS: Three themes, nine subthemes, and 24 quotes were identified. The 3 themes included the psychological response of fear, annoyance, and worrisome; social isolation leading to loneliness and physical exhaustion; and the coping strategies in adversity. Fear was the major emotional response, which was not entirely explained by the uncertainty of the disease, but also the embedded routines norms and values. Loneliness was aggravated by the depleted family and community support. Physical distancing had intensified ones physical demand on self-care, especially among those with comorbid illnesses. The use of digital tools and telecommunications maintained the social connection, but the overexposure had led to a vicious cycle of anxiety and distress. CONCLUSION: Self-isolation has disproportionately affected older individuals whose only social contact is out of the home. Online technologies can be harnessed to provide social support networks and a sense of belonging, but its adaptive and positive uses should be encouraged. Interventions can also involve more frequent telephone contact with significant others, close family and friends, voluntary organizations, or health-care professionals, or community outreach teams. Enhancing the values of older people's in calamity through active engagement may also potentially reduce the detrimental effect of social isolation.

Differential associations among social support, health promoting behaviors, health-related quality of life and subjective well-being in older and younger persons: a structural equation modelling approach.

BACKGROUND: Extensive studies have confirmed social support as a critical protective factor of people's health-related quality of life (HRQoL) and subjective well-being (SWB). However, health promoting behaviors as a potential mechanism and age differences in this mechanism has received fewer attention. This study aims to examine the associations among social support, health promoting behaviors, HRQoL and SWB in older and younger persons in Hong Kong. METHOD: A convenience sample of both younger (12-35 years old) and older persons (55 years old and above) were recruited from three non-government organizations to complete a survey. Structural Equation Model (SEM) was conducted to test both the measurement model and structural models to examine the relationship between social support, health promoting behaviors, HRQoL and SWB. Multi-group SEM was also performed and compared to test whether there were significant age differences in the pathways between the key variables. RESULTS: A final sample of 408 participants (older-persons: N = 200 (mean age: 71.63 (8.16); 180/200 female), younger-persons: N = 208 (mean age: 18.10 (5.04); 155/208 female) were included in the final analysis. Results showed that social support was positively associated with SWB directly and indirectly through health promoting behaviors for the whole sample (CFI = .95, IFI = .94, RMSEA = .07, SRMR = 0.056). Results suggested that the association between the variables differed across age samples. While social support showed a positive association with health promoting behaviors for both younger and older persons, how each of them associated with HRQoL and SWB was different. CONCLUSION: Findings suggest that the pathway which social support linked with HRQoL and SWB might differ across age groups. Age-specific strategies should be considered when promoting HRQoL and SWB among the younger and older population.

Resilience and coping strategies of older adults in Hong Kong during COVID-19 pandemic: a mixed methods study.

BACKGROUND: Despite the adverse physical health impact of COVID-19 on older adults, whether they are psychosocially vulnerable under the pandemic remains debatable. In this mixed methods study, we examined the psychosocial vulnerability of older adults relative to their younger counterparts and explored how they coped with the pandemic. METHODS: From September to October 2020, 1067 adults in Hong Kong were randomly sampled and completed a telephone survey, whereas 10 older adults were recruited for individual interviews between September 2020 and April 2021. Quantitative measurements included subjective well-being, worries about COVID-19, and changes in social capital and social interaction since the pandemic. The transcribed qualitative data were closely read and summarized using thematic analyses. RESULTS: Compared with younger adults, older adults tended to be less worried about COVID-19 infection and economic activity/livelihood, despite being slightly more worried about supplies of personal protective equipment. They also had better subjective well-being in terms of happiness and life satisfaction, with their social capital and social interaction less affected. In addition, five themes emerged from the qualitative interviews: (1) life philosophy; (2) economic security; (3) telecommunication; (4) role of community organizations and social workers; and (5) positive coping strategies. CONCLUSIONS: Older adults in this study showed better psychosocial well-being than their younger counterparts under the COVID-19 pandemic, which challenged the deeply rooted societal stereotype about the vulnerability of older adults. The stronger resilience for positive coping, technological assistance, and targeted government and community support may have protected older adults from distress during the pandemic.